Coeliac disease and malignancy

doi:10.1016/S1590-8658(02)80198-0

Digestive and Liver Disease

Volume 34, Issue 3, March 2002, Pages 229-237

https://doi.org/10.1016/S1590-8658(02)80198-0 Get rights and content

Abstract

The development of malignancy, particularly lymphoma, is the most serious complication to affect patients with coeliac disease. Although the association has been known for about 40 years, there are still gaps in our understanding. The prevalence of lymphoma and why only some coeliac patients develop this are not clear but environmental and genetic factors must be at work. Based on data from a large coeliac clinic in Derby, about 55 lymphomas per year would arise in the coeliac population of the United Kingdom, of which half would affect the small bowel. Whether patients with coeliac disease who have atypical or no symptoms at diagnosis, are at the same risk as those who are diagnosed as a result of classical symptoms as was more the case in the past, is not known. Some patients, however, do have coeliac disease and lymphoma diagnosed at the same presentation. This consideration has implications for initiating screening programmes to detect coeliac disease and thus offer patients a gluten-free diet early that would help to reduce the risk of lymphoma from developing. In this context, case-finding rather than blanket population screening is to be recommended on present evidence. Research into the role of intraepithelial lymphocytes in the genesis of lymphoma has indicated that non-responsive coeliac disease (refractory spruej and ulcerative jejunoileitis (ulcerative jejunitis) are part of the lymphoma spectrum. The diagnosis of lymphoma can be difficult and the prognosis, in general, is poor, although with modern chemotherapeutic regimes and surgery in selected cases, long-term survival is possible. The best option is to try and prevent lymphoma from arising by advising all patients to adhere to a strict gluten-free diet. Malignant complications of coeliac disease are uncommon but will continue to challenge clinicians and clinical scientists. Unravelling the mechanisms that contribute to the development of lymphoma and other tumours in coeliac disease may well contribute to a wider understanding of oncogenesis.

References (73)

O.D. Harris et al.
Malignancy in adult coeliac disease and idiopathic steatorrhea
Am J Med
(1967)
C.M. Swinson et al.
Coeliac disease and malignancy
Lancet
(1983)
H.J. Freeman et al.
Primary abdominal lymphoma. Presenting manifestations of coeliac sprite, or complicating dermatitis herpetiformis
Am J Med
(1977)
M. Blumstein et al.
Immunoproliferative small intestinal disease in an American patient with lymphoma and macroamylasaemia
Gastroenterology
(1992)
T.H. Igbal et al.
Immunoproliferative small intestinal disease or coeliac disease
Gastroenterology
(1993)
P.C. de Bruin et al.
Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa-associated lymphoid tissue localisation
Blood
(1994)
C. Cellier et al.
Abnormal intestinal intraepithelial lymphocytes in refractory sprue
Gastroenterology
(1998)
P. Isaacson et al.
Malignant histiocytosis of the intestine
Hum Pathol
(1978)
D.H. Wright et al.
Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial lymphocytes?
Lancet
(1991)
N. Brousse et al.
Is complicated celiac disease or refractory sprue an intestinal intra-epithelial cryptic T -cell lymphoma?
Blood
(1999)

F. Carbonnel et al.

Are complicated forms of celiac disease cryptic Tcell lymphomas?

Blood

(1998)

E. Bagdi et al.

Mucosal intra-epithelial lymphocytes in enteropathy-associated Tcell lymphoma, ulcerative jejunitis, and refractory celiac disease constitute a neoplastic population

Blood

(1999)

C. Matuchansky et al.

Cavitation in mesenteric lymph nodes, splenic atrophy, and a flat small intestinal mucosa

Gastroenterology

(1984)

H.J. Freeman et al.

Small bowel malignant lymphoma complicating celiac sprue and the mesenteric lymph node cavitation syndrome

Gastroenterology

(1986)

W.M. Howell et al.

HLA-DRB, -DQA, and -DQB polymorphism in coeliac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy

Hum Immunol

(1995)

M. Congia et al.

A gene dosage effect of the DQA1∗0501/DQB1∗0201 allelic combination influences the clinical heterogeneity of coeliac disease

Hum Immunol

(1994)

H.J. Freeman et al.

Multifocal small bowel lymphoma and latent coeliac sprue

Gastroenterology

(1986)

K.R. Gough et al.

Intestinal reticulosis as a complication of idiopathic steatorrhoea

Gut

(1962)

W.I. Austad et al.

Steatorrhoea and malignant lymphoma. The relationship between malignant tumours of lymphoid tissue and coeliac disease

Am J Dig Dis

(1967)

G.K.T. Holmes et al.

Coeliac disease, gluten free diet and malignancy

Gut

(1976)

Case records of the Massachussetts General Hospital

New Engl J Med

(1958)

C. O'Farrelly et al.

Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma

Br Med J

(1986)

The non-Hodgkin's Lymphoma Classification Project

A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma

Blood

(1997)

G.K.T. Holmes et al.

Malignancy as a complication of coeliac disease

H. Hin et al.

Coeliac disease in primary care: case finding study

Br Med J

(1999)

S.D. Johnson et al.

Coeliac disease detected by screening is not silent — simply unrecognized

Q J Med

(1998)

B.R.C. O'Driscoll et al.

HLA type of patients with coeliac disease and malignancy in the west of Ireland

Gut

(1982)

M. Ilyas et al.

Non-Hodgkin's lymphoma, coeliac disease, and Epstein-Barr virus: a study of 13 cases of enteropathy-associated T and B-cell lymphoma

J Pathol

(1995)

L.J. Egan et al.

Coeliac-associated lymphoma

J Clin Gastroenterol

(1995)

L. Brandt et al.

Lymphoma of the small intestine in adult coeliac disease

Acta Med Scand

(1978)

W.S. Selby et al.

Malignancy in a 19 year experience of adult coeliac disease

Dig Dis Sci

(1979)

O.H. Nielsen et al.

Non-tropical sprue. Malignant disease and mortality rate

Scand J Gastroenterol

(1995)

P. Collin et al.

Coeliac disease — associated disorders and survival

Gut

(1994)

M. Cottone et al.

Mortality and causes of death in celiac disease in a Mediterranean area

Dig Dis Sci

(1999)

A. Ferguson et al.

Coeliac disease and malignancies

Acta Paediatr

(1996)

F. Delco et al.

Celiac sprite among US Military Veterans. Associated disorders and clinical manifestations

Dig Dis Sci

(1999)

Cited by (42)

New/Revised Entities in Gastrointestinal Lymphoproliferative Disorders
2019, Surgical Pathology Clinics
Citation Excerpt :
The pathogenesis of EATL is strongly associated with celiac disease/gluten sensitive enteropathy and is a feared complication of this condition.10–14 Patients demonstrate higher levels of antiendomysial (or antitissue transglutaminase 2) antibodies, HLA-DQ2 or HLA-DQ8 alleles, and dermatitis herpetiformis,15 and demonstrate gluten sensitivity with a protective effect of gluten-free diet.4,12,16–26 Risk factors linked to EATL are duration and dose of gluten exposure, advanced age,7,23–25 and HLA-DQ2 allele homozygosity.4,23,26
T-cell/NK-cell lymphomas: A review
2007, Cancer Letters
Citation Excerpt :
Patients with known celiac disease should adhere to a gluten-free diet. Treatment with a gluten-free diet might decrease the risk of lymphoma, implicating chronic antigenic stimulation as a causal factor [85]. Small bowel perforation or obstruction, gastrointestinal bleeding, and enterocoelic fistulas are recognized complications of this disease [83].
T-cell neoplasms are a group of heterogeneous neoplasms that present a challenge in management. Accurate diagnosis and classification are necessary for proper treatment. This dilemma is exemplified by continuous upgrading of classification systems in an effort to better understand these diseases. The spectrum of management varies from observation and monitoring to prompt aggressive multimodality treatment to achieve optimal outcomes. Allogeneic transplant has been successful in a minority of cases with the possibility of cure; however this approach is still largely experimental. Molecular studies such as gene expression profiling are expected to offer exciting insight into the biology of these diseases. Novel therapeutic approaches continue to be explored, however will probably require larger clinical trials to establish their utility over the current standard.
Abdominal CT findings may suggest coeliac disease
2005, Digestive and Liver Disease
Coeliac disease is the most common gastrointestinal immunological disorder in the western countries. Many adult patients present non-specific symptoms and signs of malabsorption such as chronic diarrhoea, anaemia, weight loss and abdominal distention. In non-specific and doubtful conditions, computed tomography is often the first medical examination performed. In a clinical practice, a critical review of computed tomography signs is therefore mandatory.
To evaluate the abdominal computed tomography findings, which are useful to suggest the presence of coeliac disease in adult patients.
The computed tomography studies of 28 coeliac patients were reviewed, looking for any intestinal and extraintestinal abnormality. The computed tomography findings evaluated were: abnormalities of intestinal fold pattern, bowel dilatation, fluid and air excess, duodenal abnormalities, intestinal intussusception, bowel wall thickening, lymphadenopathy, ascites, intestinal stenosis, mesenteric vascular changes. The abdominal computed tomography of a group of 30 normal subjects was also analysed.
Intestinal fold pattern abnormalities were seen in 23/28 patients. Intestinal dilatation was seen in 21/28. Fluid excess in 18/28 and lymphadenopathy was seen in 12/28 patients; engorgement of mesenteric vessels in 7/28. Bowel wall thickening was observed in 6/28 patients and transient intussusception was observed in 6/28 patients. Increased air content within the bowel in 4/28 and ascites in 2/28 patients. Bowel dilatation together with fluid excess was observed in 18/28 patients.
None of the above mentioned abnormalities abnormalities were seen in normal subjects.
Data of the present study show that several abdominal computed tomography findings may be seen in coeliac adult patients; these findings should be taken into consideration with a high in level of suspicion by radiologists, to avoid diagnostic delay and unnecessary diagnostic and therapeutic procedures.
Celiac disease in close family members
2005, Atencion Primaria
Investigar la presencia deenfermedad celíaca (EC) entre los familiaresde primer grado de pacientes celíacos, asícomo las posibles diferencias clínicas entrefamiliares diagnosticados y sus respectivoscasos índices.
Estudio observacional, descriptivo, basado en una serie de casos.
Centro de salud y hospital.
Familiares de pacientes celíacosinscritos en la Asociación de Celíacos deAndalucía, residentes en Sevilla.
Se entrevistó a lospacientes y sus familiares y secumplimentaron 2 cuestionarios. Elprimero, dirigido a celíacos, permitióregistrar datos de la enfermedad y elsegundo, datos de filiación, enfermedadesactuales, antecedentes personales yfamiliares de todos los participantes. Seefectuó una determinación de anticuerposantiendomisio IgA (AEM IgA)exclusivamente a los familiares.
De 215 familias censadas,acudieron 56, computándose 239participantes. En los 56 pacientes, 1 porcada familia, la forma de presentación en elmomento del diagnóstico fue el síndrome dehipoabsorción. En 165 familiares estudiadosse observaron 11 casos con AEM IgApositivos y se confirmó la presencia deenfermedad celíaca en 5. De ellos, unoestaba asintomático, 3 presentaban formasatípicas de enfermedad celíaca y uno fuediagnosticado de dermatitis herpetiforme.
La mayor frecuencia deenfermedad entre los familiares de primergrado, junto con su presentación clínicaasintomática o atípica, justifican la búsquedaactiva de casos. Se considera que losmédicos de atención primaria deberíaninterrogar a estos familiares para averiguar sise les ha realizado el cribado de laenfermedad. En su defecto, a los adultos seles solicitarían los anticuerpos referidos y losniños serían remitidos a sus pediatras paratal fin.
To investigate the presence of celiac disease (CD) in close family members of celiac patients, and the possible clinical differences between family members diagnosed and their respective index cases.
Descriptive, observational study based on a series of cases.
Health centre and hospital.
Family members of celiac patients registered with the Association of Celiacs of Andalusia, based in Sevilla.
Patients and family members were interviewed and 2 questionnaires were filled in. The first, aimed at celiacs, recorded details of their disease and the second recorded personal details, current illnesses, personal history and the family members of all participants. IgA endomysium antibodies were determined only in family members.
56 of 215 families recorded took part, with 239 participants. Of the 56 patients, 1 per family, presentation at the moment of diagnosis was malabsorption syndrome. Of 165 family members studied, 11 cases with positive IgA endomysium antibodies were found and 5 actually with CD. One of these was asymptomatic, three presented with atypical forms of CD and another was diagnosed with herpetiform dermatitis.
That CD was most commonly found among close family members, along with its asymptomatic or atypical clinical presentation, justifies the active search for cases. Primary care doctors should question family members as to whether they have been tested for the disease. If not, adults should be checked for the antibodies referred to and children should be referred to their paediatricians for this purpose.
Cognitive impairment and celiac disease: Is transcranial magnetic stimulation a Trait d’Union between gut and brain?
2018, International Journal of Molecular Sciences
Neurophysiology of the "celiac brain": Disentangling gut-brain connections
2017, Frontiers in Neuroscience

View all citing articles on Scopus

View full text

MinisymposiumCoeliac disease and malignancy

Abstract

Am J Med

Lancet

Am J Med

Gastroenterology

Gastroenterology

Blood

Gastroenterology

Hum Pathol

Lancet

Blood

Blood

Blood

Gastroenterology

Gastroenterology

Hum Immunol

Hum Immunol

Gastroenterology

Intestinal reticulosis as a complication of idiopathic steatorrhoea

Gut

Steatorrhoea and malignant lymphoma. The relationship between malignant tumours of lymphoid tissue and coeliac disease

Am J Dig Dis

Coeliac disease, gluten free diet and malignancy

Gut

Case records of the Massachussetts General Hospital

New Engl J Med

Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma

Br Med J

A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma

Blood

Malignancy as a complication of coeliac disease

Coeliac disease in primary care: case finding study

Br Med J

Coeliac disease detected by screening is not silent — simply unrecognized

Q J Med

HLA type of patients with coeliac disease and malignancy in the west of Ireland

Gut

Non-Hodgkin's lymphoma, coeliac disease, and Epstein-Barr virus: a study of 13 cases of enteropathy-associated T and B-cell lymphoma

J Pathol

Coeliac-associated lymphoma

J Clin Gastroenterol

Lymphoma of the small intestine in adult coeliac disease

Acta Med Scand

Malignancy in a 19 year experience of adult coeliac disease

Dig Dis Sci

Non-tropical sprue. Malignant disease and mortality rate

Scand J Gastroenterol

Coeliac disease — associated disorders and survival

Gut

Mortality and causes of death in celiac disease in a Mediterranean area

Dig Dis Sci

Coeliac disease and malignancies

Acta Paediatr

Celiac sprite among US Military Veterans. Associated disorders and clinical manifestations

Dig Dis Sci

Minisymposium
Coeliac disease and malignancy